Fluoroquinolone derivatives are well known for their inhibitory activity on the synthesis of bacterial deoxyribonucleic acid, and consequently are good bactericides. Most fluoroquinolones are also poorly soluble in water and poor aqueous solubility of a drug can make it difficult to deliver that drug in an efficacious manner to a patient. Researchers have made various attempts to either improve the aqueous solubility of fluoroquinolones or to create suspensions of fluoroquinolone drug that can then be delivered to a patient. For example, U.S. Pat. No. 5,304,559 suggests the use of a divalent metal ion such as Cu++, Zn++, or Mg2+ and acids, to create salts that are then maintained as stable suspensions for use as parenteral or more preferably as ophthalmic formulations. U.S. Pat. No. 5,225,413 recommends the use of calcium ions and adjusting the pH to 6.5 to 7.5 to create a water soluble solution of quinolone that can be used for egg dipping.
Quinolone carboxylic acid--metal ion--acid complexes are described in U.S. Pat. No. 5,334,589 to describe compositions of quinolone carboxylic acids plus metal ions plus acid to form an acid complex that can then be used in intravenous administrations. As an added benefit, this quinolone--metal ion--acid complex is also said to have decreased venous irritation upon injection. In contrast to this suggestion, others have reported that divalent metal ions, in particular Mg2+ ions, have a pronounced inhibitory effect on an animal's uptake of quinolone, apparently the metal ion complex reduces the bioavailability of quinolones. See, S. Valisena, et. al. "Relevance of Ionic Effects on Norfloxacin Uptake by E. Coli." Biochemical Pharmacology, vol. 40. no. 3, pp. 431-436 (1990) and John S. Chapman and Nafsika H. Georgopapadakou, "Antimicrobial Agents and Chemotherapy," vol 32. no. 4, pp. 438-442, (1988).
This disclosure provides novel quinolone complexes with surprising and unexpectedly improved properties over previously disclosed compositions.